The biological properties of neurotropic viruses and their interaction with neural tissue at the cellular level will be investigated. The principal agent under study is visna virus, the cause of a progressive demyelinating disease of sheep. This virus produces a "slow" infection of the nervous system; as long as six years may pass between inoculation of the agent and the first signs of disease. Visna virus can be propagated in tissue cultures derived from sheep organs. It resembles the RNA tumor viruses in morphology and other properties including the presence of an RNA-dependent DNA polymerase (reverse transcriptase) and 60-70S single-stranded RNA as its major nucleic acid species. The biological properties of visna virus will be studied. Particular attention will be given to analysis of the virus' nucleic acid, proteins and effects on cell membranes. Hybridization studies are planned to determine if nucleic acids with sequence homology to the DNA formed by the endogenous visna virus polymerase reaction can be demonstrated in normal and diseased sheep tissues. The objectives will be to define the biochemical nature of the virus and its relationship to oncogenic viruses. Experiments will also be conducted to extend initial observations on the immunofluorescence staining observed when brain sections from patients with post-encephalitic Parkinson's disease are exposed to fluorescein-conjugated antiserum prepared against the neurotropic NWS and WS-N strains of influenza virus. Further studies with neurotropic influenza virus strains will include analysis of the protective effects of incomplete autointerfering virus particles on experimental encephalitis and influenza virus' effects on organotypic cultures derived from embryonic mouse nervous system.